Towards Gas-Phase Enzymes: Ion Chemistry for Introducing Selective Dissociation Pathways into Bio-ions

Tandem mass spectrometry has long been used as a tool to extract structural information from an analyte ion. However, the information obtained in a tandem mass spectrometry experiment is dependent on both the ion type subjected to activation and the type of dissociation method used. Several activation methods, including electron capture dissociation (ECD), electron transfer dissociation (ETD), and ultraviolet photodissociation (UVPD) have emerged with a common objective to maximize the number of sequence informative product ions. There is merit, though, in mass spectrometry-based approaches which maximize selective cleavages, serving to concentrate product ion signal into relatively few fragmentation channels or to introduce a weak-spot into a peptide or protein. Ion/ion reactions can be used as a means to transform peptide and protein ions to new ion types which demonstrate highly selective fragmentation channels. Here, the utility of introducing selective cleavages via ion/ion reactions is demonstrated. In one example, a series of proton transfer ion/ion reactions are utilized to concentrate and move the precursor ion signal into a mass-to-charge region most likely to maximize cleavages at aspartic acid and proline, aiding in low abundance protein identification. In another example, various types of ion/ion reactions are utilized to unambiguously sequence cyclic peptides in the gas-phase.